While it is likely that the etiology of Alzheimer Disease (AD) is multifactorial in the majority of cases, a significant portion is due to inherited factors which are involved in primary causation or susceptibility. Other risk factors have been proposed, including: sociological factors such as depression and education level; environmental factors such as exposure to heavy metals, head trauma and smoking; biological factors including hyperthyroidism, advanced maternal age at birth, increasing age, Down Syndrome and Parkinson disease. Clearly, the etiology of AD is complex and varied. Thus, it is important that researchers study a common group of well characterized subjects in order to facilitate the comparison of data and minimize variation due to genetic and phenotypic heterogeneity. Therefore, a primary role of the Repository is to increase the knowledge of the relative importance each of these risk factors to the development of AD by making high quality family information and biological specimens available to the research community. Close examination of the genetic heterogeneity of AD can further define the roles of sociological, environmental, physiologic and genetic factors. Significant advances have been made in the last five years in identifying AD causative and susceptibility genes. However, the four identified loci, APP, APOE, S182 and STM2 account for only approximately one half of the genetic etiology in AD, indicating that there are other genes that still need to be identified. Finding these additional loci is important and will require analysis of informative, well-characterized AD families and their biological specimens. The identification of new genes will spur further research into the pathophysiological and gene/environmental interactions in AD. The Indiana Alzheimer Disease Center's National Cell Repository was established to provide the research community with large numbers of well characterized, informative families with multiple individuals affected with Alzheimer Disease. The main goal of the Repository is to facilitate research aimed at expanding our understanding of the etiology, pathogenesis, diagnosis, treatment, prevention, and ultimately, potential cure for this disease. The Repository collects and maintains information and biological specimens on well-characterized families with AD in order to provide a resource for use in research projects and to encourage and foster the development of new avenues of AD research. Specifically, the Repository seeks to identify, recruit, and gather and maintain information from families with histories of AD. This includes pedigree information; medical records concerning the evaluation, diagnosis, and treatment of patients; documentation of the cognitive, behavioral and social consequences of AD; epidemiological and demographic data, and neuropathological diagnosis information. In conjunction with the collection of these data, the Repository seeks to collect, maintain and distribute DNA and permanent cell lines from these families and to make these samples and corresponding information available for the research of a large number of qualified investigators throughout the world., The use of common data and sample sets by various researchers employing different approaches is likely to facilitate comparison of data and the emergence of a common understanding of possible interpretations. The inherent control provided by common sample sets is particularly important in research aimed at understanding a disease with significant genetic and phenotypic heterogeneity. To this end, we have already provided over 2,700 samples to nearly 40 researchers throughout the world.